Ounpuu 2018 MiP2018
Cancers of various types consist of highly diverse populations of cells. A subset of cancer cells with stemness features, cancer stem cells (CSCs), are believed to be responsible for tumour development and resistance to chemotherapy. The mitochondrial metabolism of CSCs has been shown recently to be an important target for cancer treatment, but clinical significance of CSCs and their mitochondria properties remain unclear. Our recent study provides an evidence that adenylate kinase (AK) enzymes may serve as specific regulators of metabolic remodelling in CSC-like cells. We show that AK network is upregulated in post-operative tissues of patients with colon cancer . AK activity and expression level were increased in carcinoma derived CSC (2104 Ep) compared to normal embryonic stem cells (H9) suggesting upregulation of AK as a distinct feature of malignant transformation . Interestingly, by differentiation of colon cancer cells (Caco-2) with sodium butyrate we were able to re-establish AK homeostasis. Surprisingly, the availability of glutamine and glucose in cell culture medium was able to alter AK activity upon differentiation. Induced differentiation was also accompanied by reprogramming of energy metabolism. Although undifferentiated and differentiated cells displayed similar levels of ATP, differentiated cells had decreased levels of ATP produced by glycolysis and increased levels of ATP derived from oxidative phosphorylation. Treated cells had also increased rates of cellular respiration in the presence of butyrate in the respiratory medium. To sum up, our study introduces AK as a potential target for anti-CSCs therapies and highlight the importance of further elucidation of AK role in metabolic reprogramming of colon cancer.
Labels: MiParea: Respiration Pathology: Cancer
Organism: Human Tissue;cell: Stem cells
- National Inst Chemical Physics Biophysics, Tallinn, Estonia. - [email protected]
- Chekulayev V, Mado K, Shevchuk I, Koit A, Kaldma A, Klepinin A, Timohhina N, Tepp K, Kandashvili M, Ounpuu L, Heck K, Truu L, Planken A, Valvere V, Kaambre T (2015) Metabolic remodeling in human colorectal cancer and surrounding tissues: alterations in regulation of mitochondrial respiration and metabolic fluxes. Biochem Biophys Rep 4:111-25.
- Ounpuu L, Klepinin A, Pook M, Teino I, Peet N, Paju K, Tepp K, Chekulayev V, Shevchuk I, Koks S, Maimets T, Kaambre T (2017) 2102Ep embryonal carcinoma cells have compromised respiration and shifted bioenergetic profile distinct from H9 human embryonic stem cells. Biochim Biophys Acta 1861:2146-54.